Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration

Lingzi Wu; Lei Zhou; Jinying An; Xianfeng Shao; Hui Zhang; Chunxi Wang; Guixia Zhao; Shuang Chen; Xuexue Cui; Xinyi Zhang; Fuhua Yang; Xiaorong Li; Xiaomin Zhang

doi:10.1186/s12967-023-04228-x

Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration

J Transl Med. 2023 Jun 15;21(1):388. doi: 10.1186/s12967-023-04228-x.

Authors

Lingzi Wu^#¹, Lei Zhou^#^{2

3}, Jinying An^#¹, Xianfeng Shao⁴, Hui Zhang¹, Chunxi Wang¹, Guixia Zhao⁵, Shuang Chen¹, Xuexue Cui¹, Xinyi Zhang¹, Fuhua Yang¹, Xiaorong Li¹, Xiaomin Zhang⁶

Affiliations

¹ Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China.
² Department of Applied Biology and Chemical Technology, School of Optometry, Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Hong Kong, China.
³ Centre for Eye and Vision Research (CEVR), 17W Hong Kong Science Park, Hong Kong, China.
⁴ State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing, China.
⁵ Tangshan Eye Hospital, Tangshan, China.
⁶ Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China. xzhang08@tmu.edu.cn.

^# Contributed equally.

Abstract

Background: Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging.

Methods: Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformatics analysis was performed on the proteomic profiles of sEVs, lEVs, and plasma. Candidate biomarkers were validated in a new cohort using ELISA. Pearson correlation analysis was performed to analyze the relationship between clinical parameters and proteomic data. Connectivity map database was used to predict therapeutic agents.

Results: In total, 3,668 proteins were identified and over 3000 proteins were quantified from 278 samples. When comparing diseased group to healthy control, the proteomic profiles of the two EV subgroups were more correlated with disease than plasma. Comprehensive bioinformatics analysis highlighted potential pathogenic mechanisms for these diseases. Potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 level and mean retinal thickness. Potential therapeutic drugs were proposed, and their targets were identified.

Conclusions: This study provides a proteomic landscape of plasma and EVs involved in ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis, offers insights into disease pathogenesis, identifies valuable biomarker candidates, and proposes promising therapeutic agents.

Keywords: Biomarkers; Connectivity map; Large extracellular vesicles; Plasma; Proteomic profiles; Scleritis; Small extracellular vesicles; Uveitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Behcet Syndrome* / complications
Behcet Syndrome* / diagnosis
Extracellular Vesicles*
Humans
Proteomics
Scleritis* / etiology
Spondylitis, Ankylosing* / complications
Uveitis* / complications
Uveomeningoencephalitic Syndrome* / complications
Uveomeningoencephalitic Syndrome* / diagnosis